On November 14, 2022, the U.S. Food and Drug Administration (FDA) granted mirvetuximab soravtansine-gynx accelerated approval for patients with folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatments.1 The FDA simultaneously approved the Ventana FOLR1 (FOLR-2.1) RxDx Assay as a companion diagnostic to select patients for this indication.
Supporting Efficacy Data
Approval was supported by findings in Study 0417 (ClinicalTrials.gov identifier NCT04296890), in which 104 evaluable patients with measurable disease, who were required to have received bevacizumab, received mirvetuximab soravtansine at 6 mg/kg (based on adjusted ideal body weight) intravenously (IV) every 3 weeks until disease progression or unacceptable toxicity. Patients with corneal disorders, ocular conditions requiring ongoing treatment, grade > 1 peripheral neuropathy, or noninfectious interstitial lung disease were excluded.
An investigator-assessed objective response was observed in 33 patients (31.7%, 95% confidence interval [CI] = 22.9%–41.6%), with a complete response in 5 (4.8%). Median response duration was 6.9 months (95% CI = 5.6–9.7 months).
How It Is Used
The recommended mirvetuximab soravtansine dose is 6 mg/kg adjusted ideal body weight administered once every 3 weeks via IV infusion until disease progression or unacceptable toxicity. Use requires the presence of FRα tumor expression using an FDA-approved test.
Product labeling provides instructions on premedication to ameliorate infusion-related reactions and nausea/vomiting; pretreatment eye care; and dosage modification, including dose reduction, for adverse reactions such as keratitis/keratopathy, uveitis, pneumonitis, peripheral neuropathy, and infusion-related reactions/hypersensitivity. Use of mirvetuximab soravtansine in patients with moderate or severe hepatic impairment should be avoided.
Among 106 patients receiving mirvetuximab soravtansine in Study 0417, the most common (≥ 20%) adverse events of any grade were vision impairment (50%), fatigue (49%), nausea (40%), keratopathy (37%), abdominal pain (36%), peripheral neuropathy (33%), diarrhea (31%), constipation (30%), and dry eye (27%); cataract occurred in 18%. The most common grade 3 or 4 adverse events included keratopathy (9%), vision impairment (7%), and abdominal pain (7%). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (7%) and decreased potassium (4%). Laboratory abnormalities of any grade occurring in at least 35% of patients were increased aspartate aminotransferase (50%), increased alanine aminotransferase (39%), and decreased lymphocytes (35%).
Serious adverse events occurred in 31% of patients, most commonly intestinal obstruction (8%), ascites (4%), infection (3%), and pleural effusion (3%). Adverse events led to discontinuation of treatment in 11% of patients, the most common of which were intestinal obstruction (2%) and thrombocytopenia (2%); one patient (0.9%) discontinued treatment due to visual impairment. Fatal adverse events occurred in 2% of patients; causes included small intestinal obstruction (1%) and pneumonitis (1%).
Mirvetuximab soravtansine has a boxed warning for ocular toxicity. The agent also has warnings/precautions for pneumonitis, peripheral neuropathy, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving mirvetuximab soravtansine.
1. Elahere (mirvetuximab soravtansine-gynx) injection, for intravenous use, prescribing information, ImmunoGen, Inc, November 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761310s000lbl.pdf. Accessed November 18, 2022.